Suicide in epilepsy: psychopathology,pathogenesis, and prevention

OBJECTIVE: Death by suicide among patients with epilepsy has found scant psychiatric attention, yet it may occur at the rate reported among patients with manic-depressive illness. We aim to clarify the psychopathology and pathogenesis of suicide in epilepsy and to document an effective method of prevention.METHOD: A total of 10,739 patients with epilepsy were seen at the Epi-Care Center in Memphis from 1987 to 1999. The patients with significant psychiatric complications were evaluated systematically and treated with an increasingly effective psychopharmacologic approach.RESULTS: Five suicides were registered during the 12-year period. All occurred in patients with longstanding complex partial seizures and dysphoric disorder a short time after full control of the seizures was achieved. During the last 8years of the 12-year period, more effective pharmacotherapy of the psychiatric complications of epilepsy was used (augmented antidepressant medication), and the two suicides that still occurred had eluded this treatment. Review of earlier series confirms that suicide tends to occur particularly among patients with chronic epilepsy who have obtained good control of their seizures; suicide may occur during interictal dysphoric episodes with or without psychotic features or in a state of postictal depression.CONCLUSIONS: Suppression of seizures in longstanding epilepsy may be associated with suicidal risk. The psychotoxic effect of predominant inhibitory mechanisms appears to be the crucial pathogenetic factor in all suicides. The number of suicides in our series is a fraction of that expected based on previous reports and indicates that prevention by psychopharmacologic treatment is available.     

Value of lumbar puncture in the diagnosis of infantile epilepsy and folinic acid-responsive seizures

Seizures are one of the most frequently occurring neurologic phenomena in childhood; an inborn error of metabolism should always be considered in the diagnostic workup of patients with seizures after more common causes have been excluded. Many of the known inborn metabolic errors associated with seizures can be detected by metabolite measurement in urine or blood. It is now recognized, however, that there are several conditions in which peripheral metabolite profiles remain normal. Abnormal metabolism is indicated only by the accumulation or absence of specific metabolites within the central nervous system. Some of these disorders can be detected by in vivo magnetic resonance spectroscopy. More often, an etiology can be ascertained only by analysis of specific metabolites in cerebrospinal fluid. This review describes the utility of cerebrospinal fluid metabolite analysis in the differential diagnosis of inborn errors of metabolism that lead to infantile epilepsy. These include disorders of central nervous system energy metabolism, creatine synthesis and transport, serine biosynthesis, and glucose transport, together with defects affecting the gamma-aminobutyric acid (GABA), catecholamine, and serotonin neurotransmitter systems. In addition, information is provided regarding detection of an early-onset seizure disorder that responds to folinic acid.     

Behavior problems and parenting stress in families of three-year-old children with and without developmental delays

Children and adolescents with mental retardation are at heightened risk for mental disorder. We examined early evidence of behavior problems in 225 three-year-old children with or without developmental delays and the relative impact of cognitive delays and problem behaviors on their parents. Staff-completed Bayley Behavior Scales and parent-completed Child Behavior Checklists (CBCLs) showed greater problems in children with delays than in those without delays. Children with delays were 3 to 4 times as likely to have a total CBCL score within the clinical range. Parenting stress was higher in delayed condition families. Regression analyses revealed that the extent of child behavior problems was a much stronger contributor to parenting stress than was the child's cognitive delay.     

The combined effects of antibacterial peptide cecropin A and anti-cancer agents on leukemia cells

Anti-microbial cecropins are humoral immune peptides originally found in insects. They possess a particular function of membrane permeabilization on both gram-positive and gram-negative bacteria. Yet, they are not capable of lysing eucaryotic cells. In this experiment, we confirmed that cecropin A (CA) is a special agent able to lyse leukemia cells while exerting little toxic effect on normal lymphocytes, based on the IC50 measurements. The therapeutic index of CA ranged from 6 to 17. In contrast, chemical anti-cancer agents (ACAs) are non-specific drugs capable of damaging both cancer and normal cells. Due to the functional differences between CA and ACAs, the experiments on the combined effects of CA and ACAs were conducted in vitro. Under certain conditions, synergistic effects were found with CA/S-FU and CA/Ara-C combinations. The results suggest the need for further study into the possible application of combining anti-cancer agents with antibacterial peptides for cancer treatment.     

Multiple tristetraprolin sequence domains required to induce apoptosis and modulate responses to TNFalpha through distinct pathways

Expression of the immediate early protein tristetraprolin (TTP) is induced by numerous stimuli, including tumor necrosis factor-alpha (TNFalpha). Evidence indicates that TTP limits production of TNFalpha and other cytokines by directly binding and destabilizing their mRNAs. This effect seems to require only the conserved TTP zinc finger region, and is characteristic of the related proteins TIS11b and TIS11d. TTP, TIS11b, and TIS11d each also induce apoptosis through the mitochondrial pathway analogously to certain oncogenes, suggesting that they influence growth or survival signals. Among TTP/TIS11 proteins, TTP alone also promotes apoptosis synergistically with TNFalpha. Here we show that other regions of TTP along with the zinc fingers are required for TTP to induce apoptosis. We also demonstrate that TTP acts through an additional pathway to sensitize cells to the pro-apoptotic stimulus of TNFalpha. This modulation of TNFalpha responses specifically requires the TTP N-terminal region, which is not conserved in TIS11b or TIS11d. We conclude that the physiological functions of TTP depend upon multiple regions of the TTP protein, that TTP has diverged functionally from TIS11b and TIS11d, and that modulation of TNFalpha responses may be a unique and important aspect of TTP function.     

Individual quality of life in patients with leukaemia and lymphoma

With increasingly sophisticated chemotherapy regimes being prescribed the quality of life of cancer patients has become a key outcome measure. Little has been reported concerning the experience of patients with haematological malignancy receiving chemotherapy. The objective of this study was to evaluate the clinical usefulness of a novel quality of life measure-the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) in a sample of patients with either leukaemia or lymphoma. Fifty-one patients from the haematology clinic and in-patient unit at The Royal Devon and Exeter Hospital completed the SEIQoL-DW; in addition, each patient completed the Hospital Anxiety and Depression Scale (HADS) and a ten item questionnaire covering aspects of their treatment and satisfaction with information provided. The practical application of the SEIQoL-DW is described and two patients quality of life profiles are illustrated for comparison. The relationship between quality of life, satisfaction with information provided and psychological distress as measured by the HADS is discussed.